CZ304522B6 - C-Arylglukosidový inhibitor SGLT2, farmaceutická kompozice s jeho obsahem, farmaceutická kompozice či kombinace s jeho obsahem a použití - Google Patents

Info

Publication number

CZ304522B6

CZ304522B6 CZ2002-1285A CZ20021285A CZ304522B6 CZ 304522 B6 CZ304522 B6 CZ 304522B6 CZ 20021285 A CZ20021285 A CZ 20021285A CZ 304522 B6 CZ304522 B6 CZ 304522B6

Authority

CZ

Czechia

Prior art keywords

aryl

methyl

alkyl

ochf

agent

Prior art date

1999-10-12

Links

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• 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 18
• 229940123518 Sodium/glucose cotransporter 2 inhibitor Drugs 0.000 title claims description 18
• 150000001875 compounds Chemical class 0.000 claims abstract description 174
• 239000003112 inhibitor Substances 0.000 claims abstract description 65
• 239000003472 antidiabetic agent Substances 0.000 claims abstract description 35
• 239000003524 antilipemic agent Substances 0.000 claims abstract description 31
• WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims abstract description 29
• 239000008103 glucose Substances 0.000 claims abstract description 29
• 229940125708 antidiabetic agent Drugs 0.000 claims abstract description 28
• 206010012601 diabetes mellitus Diseases 0.000 claims abstract description 21
• 208000002249 Diabetes Complications Diseases 0.000 claims abstract description 15
• 206010012655 Diabetic complications Diseases 0.000 claims abstract description 13
• 201000001320 Atherosclerosis Diseases 0.000 claims abstract description 10
• 201000001421 hyperglycemia Diseases 0.000 claims abstract description 10
• 208000011580 syndromic disease Diseases 0.000 claims abstract description 10
• 206010060378 Hyperinsulinaemia Diseases 0.000 claims abstract description 7
• 208000008589 Obesity Diseases 0.000 claims abstract description 7
• 230000003451 hyperinsulinaemic effect Effects 0.000 claims abstract description 7
• 201000008980 hyperinsulinism Diseases 0.000 claims abstract description 7
• 208000006575 hypertriglyceridemia Diseases 0.000 claims abstract description 7
• 235000020824 obesity Nutrition 0.000 claims abstract description 7
• 238000011282 treatment Methods 0.000 claims abstract description 7
• -1 4-n-butyl Chemical group 0.000 claims description 73
• 229910052739 hydrogen Inorganic materials 0.000 claims description 56
• 229910052760 oxygen Inorganic materials 0.000 claims description 51
• 125000000041 C6-C10 aryl group Chemical group 0.000 claims description 46
• 229910052717 sulfur Inorganic materials 0.000 claims description 33
• 125000000217 alkyl group Chemical group 0.000 claims description 31
• 229910052736 halogen Inorganic materials 0.000 claims description 31
• 150000002367 halogens Chemical class 0.000 claims description 31
• 125000003118 aryl group Chemical group 0.000 claims description 28
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 28
• 125000005842 heteroatom Chemical group 0.000 claims description 27
• 125000000623 heterocyclic group Chemical group 0.000 claims description 24
• 239000001257 hydrogen Substances 0.000 claims description 24
• NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 claims description 24
• 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims description 21
• 150000002431 hydrogen Chemical class 0.000 claims description 19
• 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 19
• 239000003795 chemical substances by application Substances 0.000 claims description 18
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 18
• 230000000694 effects Effects 0.000 claims description 17
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• 125000000753 cycloalkyl group Chemical group 0.000 claims description 15
• 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 13
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• 230000000879 anti-atherosclerotic effect Effects 0.000 claims description 9
• IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 9
• 125000006376 (C3-C10) cycloalkyl group Chemical group 0.000 claims description 8
• 229940121710 HMGCoA reductase inhibitor Drugs 0.000 claims description 8
• YASAKCUCGLMORW-UHFFFAOYSA-N Rosiglitazone Chemical compound C=1C=CC=NC=1N(C)CCOC(C=C1)=CC=C1CC1SC(=O)NC1=O YASAKCUCGLMORW-UHFFFAOYSA-N 0.000 claims description 8
• VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 claims description 8
• XZWYZXLIPXDOLR-UHFFFAOYSA-N metformin Chemical compound CN(C)C(=N)NC(N)=N XZWYZXLIPXDOLR-UHFFFAOYSA-N 0.000 claims description 8
• HYAFETHFCAUJAY-UHFFFAOYSA-N pioglitazone Chemical compound N1=CC(CC)=CC=C1CCOC(C=C1)=CC=C1CC1C(=O)NC(=O)S1 HYAFETHFCAUJAY-UHFFFAOYSA-N 0.000 claims description 8
• 150000003839 salts Chemical class 0.000 claims description 8
• 239000004059 squalene synthase inhibitor Substances 0.000 claims description 8
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• 239000002220 antihypertensive agent Substances 0.000 claims description 7
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 7
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• QLJODMDSTUBWDW-UHFFFAOYSA-N lovastatin hydroxy acid Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(C)C=C21 QLJODMDSTUBWDW-UHFFFAOYSA-N 0.000 claims description 7
• 238000004519 manufacturing process Methods 0.000 claims description 7
• 229960003105 metformin Drugs 0.000 claims description 7
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 7
• ZGGHKIMDNBDHJB-NRFPMOEYSA-M (3R,5S)-fluvastatin sodium Chemical compound [Na+].C12=CC=CC=C2N(C(C)C)C(\C=C\[C@@H](O)C[C@@H](O)CC([O-])=O)=C1C1=CC=C(F)C=C1 ZGGHKIMDNBDHJB-NRFPMOEYSA-M 0.000 claims description 6
• XUKUURHRXDUEBC-KAYWLYCHSA-N Atorvastatin Chemical compound C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@@H](O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-KAYWLYCHSA-N 0.000 claims description 6
• XUKUURHRXDUEBC-UHFFFAOYSA-N Atorvastatin Natural products C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CCC(O)CC(O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-UHFFFAOYSA-N 0.000 claims description 6
• 102000004366 Glucosidases Human genes 0.000 claims description 6
• 108010056771 Glucosidases Proteins 0.000 claims description 6
• 102100031545 Microsomal triglyceride transfer protein large subunit Human genes 0.000 claims description 6
• TUZYXOIXSAXUGO-UHFFFAOYSA-N Pravastatin Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(O)C=C21 TUZYXOIXSAXUGO-UHFFFAOYSA-N 0.000 claims description 6
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• 230000029663 wound healing Effects 0.000 claims description 6
• SWLAMJPTOQZTAE-UHFFFAOYSA-N 4-[2-[(5-chloro-2-methoxybenzoyl)amino]ethyl]benzoic acid Chemical compound COC1=CC=C(Cl)C=C1C(=O)NCCC1=CC=C(C(O)=O)C=C1 SWLAMJPTOQZTAE-UHFFFAOYSA-N 0.000 claims description 5
• 229940123208 Biguanide Drugs 0.000 claims description 5
• DTHNMHAUYICORS-KTKZVXAJSA-N Glucagon-like peptide 1 Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1N=CNC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 DTHNMHAUYICORS-KTKZVXAJSA-N 0.000 claims description 5
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• BOVGTQGAOIONJV-BETUJISGSA-N 1-[(3ar,6as)-3,3a,4,5,6,6a-hexahydro-1h-cyclopenta[c]pyrrol-2-yl]-3-(4-methylphenyl)sulfonylurea Chemical compound C1=CC(C)=CC=C1S(=O)(=O)NC(=O)NN1C[C@H]2CCC[C@H]2C1 BOVGTQGAOIONJV-BETUJISGSA-N 0.000 claims description 4
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